We measured arteriovenous (a-v) differences in concentrations of tumour necrosis factor-( (TNF() and interluekin-6 (IL-6) across a sucutaneous adipose tissue bed in the post-absorptive state in 39 subjects (22F17M; median {interquartile range age 36 {26-48 yrs; body mass index (BMI) 31.8 [22.3-38.7 kg.m-2; percent body fat 28.7 {17.6-50.7 %). Glycerol release from fat cells can be studied by stable isotope dilution mass spectrometry and is a marker of lipolysis. A sub-group of 8 subjects had a-v differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening - 19 ate a high carbohydrate meal around 1300 hrs; 11 continued to fast. We found a greater than two-fold increase in IL-6 concentrations across the adipose tissue bed (arterial 2.27 {1.42-3.53 pg.ml-1; venous 6.71 {3.36-9.62 pg.ml-1, p<0.001), but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with BMI and percent bo dy fat. Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 hrs) both in subjects who had extended their fasting and in subjects who had eaten. Neither deep forearm nor subcutaneous adipose tissue consistently released TNF(. Although both IL-6 and TNF( are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF( is not released by this subcutaneous depot. In contrast IL-6 is released from the depot, and is thereby able to signal systemically.